TY - JOUR
T1 - A possible mechanism for the decrease in serum thyroxine level by a 2,3,7,8-tetrachlorodibenzo-p-dioxin-like polychlorinated biphenyl congener, 3,3′,4,4′,5-pentachlorobiphenyl in mice
AU - Kato, Yoshihisa
AU - Haraguchi, Koichi
AU - Kubota, Makiko
AU - Seto, Yoshiki
AU - Okura, Takashi
AU - Ikushiro, Shin Ichi
AU - Koga, Nobuyuki
AU - Yamada, Shizuo
AU - Degawa, Masakuni
PY - 2010/1
Y1 - 2010/1
N2 - Serum total thyroxine (T4) and free T4 levels were markedly decreased 7 days after treatment with 3,3′,4,4′,5- pentachlorobiphenyl (CB126) (2.5 mg/kg i.p.) in 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD)-sensitive C57BL/6 mice but not in TCDD-resistant DBA/2 mice. At the same time, the level and activity of hepatic T4-UDP- glucuronosyltransferase (T4-UGT) were significantly increased in C57BL/6 mice but not in DBA/2 mice. Furthermore, the amounts of biliary [ 125I]T4 and [125I]T4 glucuronide after injection of [125I]T4 were increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. Clearance of [ 125I]T4 from serum was also promoted by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. On the other hand, no significant changes in the steady-state volumes of distribution of [125I]T 4 and in the concentration ratio (Kp value) of the liver to serum by CB126 pretreatment were observed in either strain of mice. Because liver weight was increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice, hepatic total [125I]T4 was increased only in C57BL/6 mice. The present findings indicate that CB126-mediated decrease in serum T4 occurs through the increase in hepatic T4-UGT and the enhanced accumulation of hepatic T4 along with development of liver hypertrophy.
AB - Serum total thyroxine (T4) and free T4 levels were markedly decreased 7 days after treatment with 3,3′,4,4′,5- pentachlorobiphenyl (CB126) (2.5 mg/kg i.p.) in 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD)-sensitive C57BL/6 mice but not in TCDD-resistant DBA/2 mice. At the same time, the level and activity of hepatic T4-UDP- glucuronosyltransferase (T4-UGT) were significantly increased in C57BL/6 mice but not in DBA/2 mice. Furthermore, the amounts of biliary [ 125I]T4 and [125I]T4 glucuronide after injection of [125I]T4 were increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. Clearance of [ 125I]T4 from serum was also promoted by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice. On the other hand, no significant changes in the steady-state volumes of distribution of [125I]T 4 and in the concentration ratio (Kp value) of the liver to serum by CB126 pretreatment were observed in either strain of mice. Because liver weight was increased by CB126 pretreatment in C57BL/6 mice but not in DBA/2 mice, hepatic total [125I]T4 was increased only in C57BL/6 mice. The present findings indicate that CB126-mediated decrease in serum T4 occurs through the increase in hepatic T4-UGT and the enhanced accumulation of hepatic T4 along with development of liver hypertrophy.
UR - https://www.scopus.com/pages/publications/73149105082
U2 - 10.1124/dmd.109.029348
DO - 10.1124/dmd.109.029348
M3 - 記事
C2 - 19786508
AN - SCOPUS:73149105082
SN - 0090-9556
VL - 38
SP - 150
EP - 156
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 1
ER -